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Antimicrobial Agents and Chemotherapy, March 2004, p. 799-803, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.799-803.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

New Findings on the Structure-Phototoxicity Relationship and Photostability of Fluoroquinolones with Various Substituents at Position 1

Norihiro Hayashi,1* Yoshihiro Nakata,2 and Akira Yazaki1

Institute for Medical Research, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195,1 Department of Pharmacology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan2

Received 13 March 2003/ Returned for modification 6 September 2003/ Accepted 15 November 2003

The present study examined the phototoxicities of a series of 7-(3-aminopyrrolidinyl) quinolones containing various substituents at position 1 (in which the substituent at R8 is a hydrogen or a halogen) by use of a mouse model. For the 7-(3-aminopyrrolidinyl) quinolones with a halogen atom at position 8, well-known substituent groups such as a cyclopropyl, an ethyl, or a difluorophenyl at position 1 were found to be responsible for severe phototoxicity. However, when an aminodifluorophenyl or an isoxazolyl group was placed at position 1, even 8-halogeno quinolones were found to be mildly phototoxic. This is the first report of 8-halogeno quinolones that are not severely phototoxic. Two structurally similar 8-chloro quinolones (the 1-aminodifluorophenyl 8-chloro quinolone and the 1-difluorophenyl 8-chloro quinolone) were investigated further. The former was mildly phototoxic; the latter was severely phototoxic. We demonstrate that these two 8-chloro quinolones have practically the same areas under the concentration-time curves from 0 to 4 h in auricular tissue, suggesting that the mild phototoxicity is not due to pharmacokinetic instability. The rates of UV photodegradation of these compounds were also measured. We found that these two quinolones photodegrade at similar rates, suggesting that the mild phototoxicity is not attained through increased photostability. In conclusion, the phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 but also by that at position 1 (a new finding from this study). We also discovered a mildly phototoxic 8-chloro quinolone which did not have increased photostability.

* Corresponding author. Mailing address: Institute for Medical Research, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Kodacho, Takatagun, Hiroshima 739-1195, Japan. Phone: 81-826-45-2331. Fax: 81-826-45-4351. E-mail: hayashi_n{at}wakunaga.co.jp.

Antimicrobial Agents and Chemotherapy, March 2004, p. 799-803, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.799-803.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mehlhorn, A. J, Brown, D. A (2007). Safety Concerns with Fluoroquinolones. The Annals of Pharmacotherapy 41: 1859-1866 [Abstract] [Full Text]  


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